<i>LGI1</i>
            microdeletion in autosomal dominant lateral temporal epilepsy

Fanciulli, Manuela; Santulli, Lia; Errichiello, Luca; Barozzi, Chiara; Tomasi, Luciana; Rigon, Laura; Cubeddu, Tiziana; Falco, Arturo de; Michelucci, Roberto; Uzzau, Sergio; Striano, Salvatore; Falco, Fabrizio Antonio de; Striano, Pasquale; Nobile, Carlo

doi:10.1212/wnl.0b013e3182518328

Cited by 26 publications

(18 citation statements)

References 10 publications

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“…In our series of 35 Italian ADLTE families (33 described in Michelucci et al, 2013, and 2 in this study), we identified 12 LGI1-mutated families (34%), each segregating a different mutation. Ten of 35 families (28%) segregated LGI1 point mutations (9 reviewed in Michelucci et al, 2013, and 1 described in this study), whereas 2 (6%) had microdeletions (Fanciulli et al, 2012;and present study). This ratio (5:1) between point mutations and gene rearrangements is in line with that found in other genes for Mendelian disorders (Botstein and Risch, 2003).…”

Section: Discussionsupporting

confidence: 49%

“…De novo LGI1 mutations have been detected in a small proportion (about 1%) of sporadic lateral temporal epilepsy (LTE) patients (Bisulli et al, 2004a;Michelucci et al, 2007). Nearly all LGI1 mutations are point mutations, either nonsynonymous or splice-site mutations or short indels, distributed along the gene length Ho et al, 2012), and only a single microdeletion spanning the first four exons has been reported (Fanciulli et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Autosomal dominant lateral temporal epilepsy (ADLTE): Novel structural and single-nucleotide LGI1 mutations in families with predominant visual auras

et al. 2015

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Section: Discussionsupporting

confidence: 49%

Section: Introductionmentioning

confidence: 99%

Autosomal dominant lateral temporal epilepsy (ADLTE): Novel structural and single-nucleotide LGI1 mutations in families with predominant visual auras

et al. 2015

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“…High‐density single nucleotide polymorphism (SNP) arrays that include nonpolymorphic probes optimized for copy number measurements can detect CNVs as small as 10 kb . By using these high‐density SNP platforms, we recently identified the first LGI1 microdeletion associated with ADLTE …”

mentioning

confidence: 99%

Copy number variations and susceptibility to lateral temporal epilepsy: A study of 21 pedigrees

Fanciulli¹,

Pasini

Malacrida

et al. 2014

Epilepsia

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SUMMARYObjective: Autosomal dominant lateral temporal epilepsy (ADLTE) is a focal epileptic syndrome characterized by auditory or aphasic auras. Mutations in the LGI1 gene account for <50% of ADLTE families. To identify copy number variants (CNVs) related to ADLTE, we examined a collection of ADLTE families without LGI1 mutations. Methods: Twenty-one families were included based on a history of focal seizures with auditory and/or receptive aphasic symptoms in two or more individuals, absence of brain abnormalities, and negative LGI1 test. DNA suitable for single nucleotide polymorphism-array analysis was genotyped using the high-density HumanOmni1-Quad v1.0 beadchip (Illumina). CNVs were inferred using the PennCNV algorithm. Selected CNVs were validated by real-time quantitative polymerase chain reaction (qPCR). Results: We analyzed 62 affected and 114 unaffected members of our study families and identified a total of 11,214 CNVs, corresponding to 1,890 unique regions with an average size of 67.3 kb. Most CNVs were <50 kb, whereas a small proportion (1.2%) exceeded 500 kb. We identified 12 rare CNVs that segregated with lateral temporal epilepsy in single families. Particularly, we found rare microdeletions within or near two genes, RBFOX1 and NRXN1, previously shown to harbor deletions associated with idiopathic generalized epilepsy, and a microduplication in the proximal region of chromosome 1q21.1, where duplications have been associated with various neurodevelopmental disorders and epilepsy. We also found numerous polymorphic CNVs in the affected members of one or more families, including a deletion of the PCDHA8/10 genes, which was enriched in the patients of our family cohort. Significance: Our results provide clues on genes for susceptibility to ADLTE, particularly in those families where the inheritance pattern is less compatible with autosomal dominance. Some of these genes also confer risk for other epilepsy syndromes.

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“…The 12 LGI1 mutated families have been described in detail elsewhere [2], [5], [7], [8], [9], [10], [11], [12], [13] whereas the 7 pedigrees with RELN mutations have been reported limited only to the genetic findings [6].…”

Section: Methodsmentioning

confidence: 99%

The clinical phenotype of autosomal dominant lateral temporal lobe epilepsy related to reelin mutations

Michelucci

Pulitano

Bonaventura

et al. 2017

Epilepsy & Behavior

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ObjectiveTo describe the clinical phenotype of 7 families with Autosomal Dominant Lateral Temporal Lobe Epilepsy (ADLTE) related to Reelin (RELN) mutations comparing the data with those observed in 12 LGI1-mutated pedigrees belonging to our series.MethodsOut of 40 Italian families with ADLTE, collected by epileptologists participating in a collaborative study of the Commission for Genetics of the Italian League against Epilepsy encompassing a 14-year period (2000–2014), 7 (17.5%) were found to harbor heterozygous RELN mutations. The whole series also included 12 (30%) LGI1 mutated families and 21 (52.5%) non-mutated pedigrees. The clinical, neurophysiological, and neuroradiological findings of RELN and LGI1 mutated families were analyzed.ResultsOut of 28 affected individuals belonging to 7 RELN mutated families, 24 had sufficient clinical data available for the study. In these patients, the epilepsy onset occurred at a mean age of 20 years, with focal seizures characterized by auditory auras in about 71% of the cases, associated in one-third of patients with aphasia, visual disturbances or other less common symptoms (vertigo or déjà-vu). Tonic–clonic seizures were reported by almost all patients (88%), preceded by typical aura in 67% of cases. Seizures were precipitated by environmental noises in 8% of patients and were completely or almost completely controlled by antiepileptic treatment in the vast majority of cases (96%). The interictal EEG recordings showed epileptiform abnormalities or focal slow waves in 80% of patients, localized over the temporal regions, with marked left predominance and conventional 1,5T MRI scans were not contributory.By comparing these findings with those observed in families with LGI1 mutations, we did not observe significant differences except for a higher rate of left-sided EEG abnormalities in the RELN group.SignificanceHeterozygous RELN mutations cause a typical ADLTE syndrome, indistinguishable from that associated with LGI1 mutations.

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LGI1 microdeletion in autosomal dominant lateral temporal epilepsy

Cited by 26 publications

References 10 publications

Autosomal dominant lateral temporal epilepsy (ADLTE): Novel structural and single-nucleotide LGI1 mutations in families with predominant visual auras

Autosomal dominant lateral temporal epilepsy (ADLTE): Novel structural and single-nucleotide LGI1 mutations in families with predominant visual auras

Copy number variations and susceptibility to lateral temporal epilepsy: A study of 21 pedigrees

The clinical phenotype of autosomal dominant lateral temporal lobe epilepsy related to reelin mutations

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